Müllerian adenosarcoma (MA) is an uncommon biphasic neoplasm of the female genital tract, representing 5-10% of uterine mesenchymal neoplasms (Major et al. 1993, Abeler et al. 2009). MA is composed of malignant stroma and benign Müllerian epithelium (Clement and Scully 1974, Fox et al. 1979, Clement and Scully 1990). The majority of MA arise in the uterine corpus but it has also been well-described arising in the cervix, ovary, vagina, and sites outside the female genital tract (likely arising from endometriosis) (Clement and Scully 1978, Jones and Lefkowitz 1995, Eichhorn et al. 2002). Uterine MA often presents as a polypoid mass occupying the endometrial cavity, and may be multifocal. Histologically, it is characterized by well-developed, broad leaf-like glandular architecture, with periglandular stromal condensation, cytologic atypia, and mitoses (1-5). Although many MA are clinically indolent, the presence of sarcomatous overgrowth (SO, defined as >25% of the tumor composed of sarcoma without an epithelial component), is strongly associated with a substantial risk of recurrence and metastasis (Clement 1989, Gallardo and Prat 2009). Uterine MA lacking SO are relatively indolent, having a 20-30% recurrence rate (1, 2, 5), but low rate of distant metastasis, and low overall mortality (1, 2, 4, 5). Such tumors are treated primarily with surgery (5), whereas those with SO are often treated with chemotherapy, radiation therapy, or both. An additional histologic parameter that may indicate a worse prognosis is deep (greater than 50%) myometrial invasion (1, 2, 6, 7).
Immunohistochemically, CD10 is considered to be the most commonly recognized positive marker for MA (8-14); however, WT-1, ER, and PR are also often expressed (8-12). SMA (12-14) and desmin (12-14) are variably expressed. In MA, particularly those with SO, the proliferative index is elevated (11, 12), and frequently accompanied by loss of CD10, WT-1, PR, and ER expression (8-12). Some studies have found that p53 is aberrantly overexpressed in a few MA with SO (11, 15, 16). Despite these efforts, no reliable immunohistochemical marker distinguishes MA from potentially morphologically similar tumors, namely carcinosarcoma, endometrial stromal neoplasms, benign uterine polyps, so-called “adenofibroma,” embryonal rhabdomyosarcoma, and occasionally, smooth muscle tumors. Unfortunately, there exists no known recurrent cytogenetic abnormality, or molecular diagnostic test to serve as an adjunct to the hematoxylin and eosin (H&E) based diagnosis, so presently, the diagnosis is essentially made on histologic grounds without any reliable confirmatory immunohistochemical or molecular/genetic test.